enfortumab vedotin + pembrolizumab + cisplatin

This is a **combination regimen** of three drugs: enfortumab vedotin, pembrolizumab, and cisplatin. - **Enfortumab vedotin** is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting Nectin-4 (a cell adhesion protein highly expressed in urothelial carcinoma) conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent. It works by binding to Nectin-4–expressing cells, causing internalization and release of MMAE, which induces cell cycle arrest and apoptotic cell death[4]. - **Pembrolizumab** is a programmed death 1 (PD-1) immune checkpoint inhibitor. It blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2), promoting T-cell–mediated immune responses against tumor cells[4]. - **Cisplatin** is a platinum-based chemotherapy agent. It forms DNA crosslinks and adducts, interfering with DNA replication and transcription, ultimately leading to apoptosis of rapidly dividing tumor cells. This specific triple combination is under investigation and use in muscle-invasive or metastatic urothelial carcinoma (bladder cancer), though the most prominent approved and studied combinations to date are enfortumab vedotin plus pembrolizumab (without cisplatin)[1][2][3][4][6][7]. Cisplatin is often part of standard-of-care chemotherapy regimens but is not always included with newer targeted/immunotherapy combinations due to eligibility criteria (e.g., renal function, hearing loss).